The present invention is directed to various methods and products for using mesenchymal stem cells (MSCs).
In accordance with an aspect of the present invention, an animal is treated with mesenchymal stem cells wherein the mesenchymal stem cells are obtained from an animal other than the animal being treated, i.e. the mesenchymal stem cells are not autologous.
More particularly, in accordance with an aspect of the invention, a patient is treated with allogeneic human mesenchymal stem cells. As the term is used herein, an allogeneic human mesenchymal stem cell is a mesenchymal stem cell obtained from a human other than the intended recipient of the mesenchymal stem cells.
Although the mesenchymal stem cells express surface MHC molecules, applicants have found that the mesenchymal stem cells are immunologically neutral and therefore can be used as described herein without inducing an adverse immune response in the recipient of the cells.
In addition, applicants have found that the donor of the mesenchymal stem cells need not be xe2x80x9cmatchedxe2x80x9d to the recipient.
In accordance with the present invention, it has been discovered that mesenchymal stem cells are xe2x80x9cinvisiblexe2x80x9d to the immune system. Normally, co-culturing cells from different individuals (allogeneic cells) results in T cell proliferation, manifested as a mixed lymphocyte reaction (MLR). However, when human mesenchymal stem cells are contacted with allogeneic T lymphocytes, in vitro, they do not generate an immune response by the T cells, i.e., the T cells do not proliferate, indicating that T cells are not responsive to mismatched mesenchymal stem cells. This discovery was unexpected because human mesenchymal stem cells express all of the surface molecules that render them immunogenic, i.e., they express allogeneic class I and class II MHC molecules.
It has also been discovered that mesenchymal stem cells actively reduce the allogeneic T cell response in mixed lymphocyte reactions in a dose dependent manner. It has further been discovered that mesenchymal stem cells from different donors do not exhibit specificity of reduced response with regard to MHC type. Thus, mesenchymal stem cells need not be MHC matched to a target cell population in the mixed lymphocyte reaction in order to reduce the proliferative response of alloreactive T cells to mesenchymal stem cells.